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Effects of the endothelin receptor antagonist bosentan on hemodynamics and exercise capacity in Japanese patients with mildly symptomatic pulmonary arterial hypertension

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Abstract

Pulmonary arterial hypertension (PAH) trial has mostly enrolled patients with World Health Organization functional class (WHO FC) III or IV. However, PAH is rapidly progressive in nature even in patients with less severe forms at diagnosis. Following the recent studies in Western population, here we assessed the efficacy of bosentan in Japanese patients with WHO FCII PAH. In this open-label trial, bosentan 125 mg twice daily was administered for 12 weeks in 16 patients, and a hemodynamic evaluation was performed. Treatment was continued for a further 12 weeks, where the effect on exercise capacity was assessed in 13 patients. In 16 patients, mean pulmonary arterial pressure decreased from 40.4 ± 10.4 to 35.6 ± 12.6 mmHg (p = 0.018) and cardiac index increased from 2.54 ± 0.73 to 2.96 ± 0.82 L/min/m2 (p = 0.023). Thus, pulmonary vascular resistance decreased from 792 ± 565 to 598 ± 558 dyn·sec/cm5 (p = 0.006). In 13 patients followed up for 24 weeks, 6-min walking distance increased from baseline at Week 12 (p = 0.003) and Week 24 (p = 0.011). All patients were mildly symptomatic at baseline with dyspnea index (Borg scale) of 2.50 ± 1.58 and the specific activity scale (SAS) of 5.0 ± 1.4 METs. These values remained unchanged throughout the study. These results suggest that bosentan treatment was beneficial for Japanese patients with WHO FC II PAH and treatment should be started in the early stage of the disease.

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Acknowledgments

This study was funded and supported by Actelion Pharmaceuticals Japan Ltd.

Conflict of interest

Dr. Sasayama has received consultant fees from Actelion Pharmaceuticals Japan Ltd. Drs. Hatano, Yamada, Fukuda, Kuwana, Nakanishi and Saji have received lecture fees from Actelion Pharmaceuticals Japan Ltd. Other investigators have no conflict of interest.

Ethical standards

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients included in the study.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Masaru Hatano

  2. Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan

    Hidehiro Yamada

  3. Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

    Keiichi Fukuda

  4. Department of Cardiovascular Medicine, Tokai University School of Medicine, Kanagawa, Japan

    Koichiro Yoshioka

  5. Department of Hematology and Rheumatology, Kinki University Faculty of Medicine, Osaka, Japan

    Masanori Funauchi

  6. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Masataka Kuwana

  7. Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan

    Masataka Sata

  8. Division of Cardiology, Kinki University Faculty of Medicine, Osaka, Japan

    Mitsugu Taniguchi

  9. Division of Pulmonary Circulation, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan

    Norifumi Nakanishi

  10. Department of Respiratory Medicine, National Hospital Organization Ibaraki-Higashi National Hospital, Ibaraki, Japan

    Takefumi Saito

  11. Department of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan

    Tsutomu Saji

  12. Kyoto University, Kyoto, Japan

    Shigetake Sasayama

Authors
  1. Masaru Hatano
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  2. Hidehiro Yamada
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  3. Keiichi Fukuda
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  4. Koichiro Yoshioka
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  5. Masanori Funauchi
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  6. Masataka Kuwana
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  7. Masataka Sata
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  8. Mitsugu Taniguchi
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  9. Norifumi Nakanishi
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  10. Takefumi Saito
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  11. Tsutomu Saji
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  12. Shigetake Sasayama
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Correspondence to Masaru Hatano.

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Hatano, M., Yamada, H., Fukuda, K. et al. Effects of the endothelin receptor antagonist bosentan on hemodynamics and exercise capacity in Japanese patients with mildly symptomatic pulmonary arterial hypertension. Heart Vessels 30, 798–804 (2015). https://doi.org/10.1007/s00380-014-0544-1

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  • DOI: https://doi.org/10.1007/s00380-014-0544-1

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